This study will evaluate the efficacy, safety and tolerability, as well as PK/PD of OCA in eligible pediatric participants with biliary atresia with successful hepatoportoenterostomy (HPE, also known as a Kasai portoenterostomy). The double-blind period comprises of 2 phases: dose titration phase and age expansion treatment phase.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
28
OCA will be administered.
Matching Placebo will be administered.
Queensland Childrens Hospital
South Brisbane, Queensland, Australia
Women's and Children's Hospital
North Adelaide, South Australia, Australia
Royal Childrens Hospital
Parkville, Victoria, Australia
Alberta Childrens Hospital
Calgary, Alberta, Canada
Stollery Children's Hospital
Edmonton, Alberta, Canada
Children's Hospital, Zhejiang University School of Medicine
Hangzhou, Zhejiang, China
Guangzhou Women And Childrens Medical Center
Guangzhou, China
Children's Hospital of Fudan University
Shanghai, China
Childrens Hospital of Shanghai
Shanghai, China
Children's Hospital of Shanxi
Taiyuan, China
...and 14 more locations
Number of Participants With Composite Liver-Related Clinical Events
Number of participants experiencing any of the following: All-cause death; Liver transplantation; Hospitalization (≥24 hours) for variceal bleeding, hepatic encephalopathy, or spontaneous bacterial peritonitis; Clinically relevant ascites requiring therapeutic paracentesis have been presented. No clinical outcome events were reported at the time of the study termination; hence It was not possible to conduct the planned primary efficacy analysis.
Time frame: Up to Week 48
Change From Baseline in Pediatric End-stage Liver Disease (PELD) Score
The Pediatric End-stage Liver Disease (PELD) score is a scale used to assess the severity of chronic liver disease in pediatric participants younger than 12 years of age. The total PELD score ranges from negative values to positive values, with no absolute minimum or maximum, with higher scores indicating more severe liver disease and greater urgency for liver transplantation. The score is calculated using total bilirubin, international normalized ratio (INR), albumin, age at listing, and growth failure. Baseline was defined as the last assessment prior to first study drug administration. Change from baseline was calculated as the last post-baseline value minus the baseline value. A negative change from baseline indicates improvement, while a positive change indicates worsening.
Time frame: Baseline and up to Week 48
Change From Baseline in Model of End-stage Liver Disease With Sodium (MELD-NA) Score
The Model of End-stage Liver Disease with Sodium (MELD-Na) score is a scale used to assess the severity of chronic liver disease in participants 12 years of age and older, ranging from 6 (less ill) to 40 (gravely ill). Higher scores indicate more severe liver disease and greater urgency for liver transplantation. The score is derived from total bilirubin, serum creatinine, INR, and serum sodium. Baseline was defined as the last assessment prior to first study drug administration. Change from baseline was calculated as the last post-baseline value minus the baseline value. A negative change from baseline indicates improvement, while a positive change indicates worsening.
Time frame: Baseline and up to Week 48
Percentage of Participants With Improvement in GGT and Direct Bilirubin (Composite Responder Endpoint)
Participants were considered responders if both of the following criteria were met at EOS: ≥40% reduction from baseline in Gamma Glutamyl Transferase (GGT), and ≥25% reduction from baseline in direct (conjugated) bilirubin. Participants with missing values were considered non-responders.
Time frame: Up to Week 48
Change From Baseline in GGT
Blood samples were collected to assess GGT levels. Baseline was defined as the last assessment prior to first study drug administration. Change from baseline was computed by subtracting the baseline value from the post-baseline value, with a positive change indicating improvement.
Time frame: Baseline and up to Week 48
Change From Baseline in Total and Direct (Conjugated) Bilirubin
Blood samples were collected to assess direct bilirubin levels. Baseline was defined as the last assessment prior to first study drug administration. Change from baseline was computed by subtracting the baseline value from the post-baseline value, with a positive change indicating improvement.
Time frame: Baseline and up to Week 48
Change From Baseline in Endogenous Bile Acids
Plasma samples were collected to assess endogenous bile acids. Baseline was defined as the last assessment prior to first study drug administration. Change from baseline was computed by subtracting the baseline value from the post-baseline value, with a positive change indicating improvement.
Time frame: Baseline and up to Week 48
Change From Baseline in Liver Stiffness as Assessed by Transient Elastography
Liver stiffness was measured using ultrasound elastography. Baseline was defined as the last assessment prior to first study drug administration. Change from baseline was computed by subtracting the baseline value from the post-baseline value, with a positive change indicating improvement.
Time frame: Baseline and up to Week 48
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Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs
TEAEs were defined as adverse events that were reported or worsened on or after the first dose of study treatment. Serious adverse events are adverse events resulting in death, are immediately life threatening, requires in-patient hospitalization or prolongation of existing hospitalization, or results in persistent or significant disability/incapacity.
Time frame: Up to Week 48
Change From Baseline in Plasma Levels of Fat-Soluble Vitamin D
Plasma samples were collected to assess levels of fat-soluble vitamins D. Baseline was defined as the last assessment prior to first study drug administration. Change from baseline was computed by subtracting the baseline value from the post-baseline value, with a positive change indicating improvement.
Time frame: Baseline and Week 48
Change From Baseline in Plasma Levels of Fat-Soluble Vitamin K
Plasma samples were collected to assess levels of fat-soluble vitamin K. Baseline was defined as the last assessment prior to first study drug administration. Change from baseline was computed by subtracting the baseline value from the post-baseline value, with a positive change indicating improvement.
Time frame: Baseline and Week 48